A clinimetric assessment of the validity and reliability of 3D technology for scar surface area measurement.

INTRODUCTION: The quality of scars has become an important outcome of burn care. Objective scar assessment through scar surface area measurement enables quantification of scar formation and evaluation of treatment efficacy. 3D technology has proven valid and reliable but often remains cumbersome, expensive, and time-consuming. 3D technology with depth sensors on mobile devices has become available and might surpass these limitations. This study provides a clinimetric assessment of the validity and reliability of a 3D system with a depth sensor for scar surface area measurement. METHODS: A technology involving a depth sensor mounted on a mobile device was used. Images and analyses were made with a custom-made software application. A standardized one-keyframe image capturing procedure was followed. To assess validity, stickers with predefined dimensions (8.01 cm2 - 77.70 cm2) were imaged in a single observer setting on various body parts of healthy volunteers. To assess reliability, hypertrophic scars, keloids, and normotrophic scars were imaged and rated by two observers independently. Data are expressed as mean (+/-SD), Coefficient of Variation (CV), Intraclass Correlation Coefficients (ICC), and Limits of Agreements (LoA). RESULTS: Eighty stickers placed on 20 healthy volunteers showed validity with CV between 0.62%- 1.67% for observer A and 0.75%- 1.19% for observer B. For the reliability study, 69 scars on 36 patients were included. Mean scar surface area ranged from 0.83 cm2 to 155.59 cm2. Mean scar surface area measurement was 13.83 cm2 (SD 23.06) for observer A and 13.59 cm2 (SD 23.31) for observer B. Adjusted interobserver CV for trained observers is estimated as 5.59%, with corresponding LoA = 0 ± 0.15 x mean surface area. Interobserver ICCs were 0.99-1.00. CONCLUSION: This 3D technology with a depth sensor for measuring scar surface area provides valid and reliable data and thereby surpasses expensive and time-consuming 3D cameras.

Clinical predictors of escalating care in hepatic and renal cyst infection in autosomal dominant polycystic kidney and liver disease.

BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.

In vitro culture conditions affecting minimal inhibitory concentration of bedaquiline against M. tuberculosis.

OBJECTIVES: In developing a standardized drug susceptibility test for bedaquiline, it is very important to know which parameters might impact its activity in vitro and result in false resistance of the bacterium to bedaquiline. We aimed to assess the impact of different in vitro conditions on the minimal inhibitory concentration (MIC) of bedaquiline against Mycobacterium tuberculosis H37Rv reference strain. METHODS: The MIC of M. tuberculosis H37Rv strain was determined under different conditions such as inoculum size, pH, temperatures, log and stationary phase cultures, protein concentration, Tween 80 concentration, and labware plastics. RESULTS: Increases in bedaquiline MIC were observed with variations in inoculum size for M. tuberculosis H37Rv on agar or in broth, in protein concentration and labware plastics on agar, and with variations in pH and Tween 80 concentrations in broth. CONCLUSIONS: In order to obtain reproducible MIC results, bedaquiline MIC should be assessed using polystyrene plates or tubes, at pH 7, with a Tween 80 concentration of 0.02%, without protein enrichment and with an inoculum size up to 10(7) colony-forming unit (CFU)/mL on 7H11 agar or with 10(5)CFU/mL in 7H9 broth.

Somatostatin analogues improve health-related quality of life in polycystic liver disease: a pooled analysis of two randomised, placebo-controlled trials.

BACKGROUND: Polycystic liver disease is associated with impaired health-related quality of life (HRQL). Somatostatin analogues reduce hepatomegaly in polycystic liver disease. AIM: To determine whether somatostatin analogues improve HRQL and to identify factors associated with change in HRQL in polycystic liver disease. METHODS: We pooled data from two randomized, double-blind, placebo-controlled trials that evaluated HRQL using the Short-Form 36 (SF-36) in 96 polycystic liver disease patients treated 6-12 months with somatostatin analogues or placebo. The SF-36 contains a summarizing physical and mental component score and was administered at baseline and at the end of treatment. We used random effect models to delineate the effect of somatostatin analogues on HRQL. We determined the effect of demographics, height-adjusted liver volume, change in liver volume, somatostatin analogue-associated side effects with change in HRQL. In patients with autosomal dominant polycystic kidney disease, we estimated the effect of height-adjusted kidney volume and change in kidney volume in relation to HRQL. RESULTS: Physical component scores improved with somatostatin analogues, but remained unchanged with placebo (3.41 ± 1.29 vs. -0.71 ± 1.54, P = 0.044). Treatment had no impact on the mental component score. Large liver volume was independently associated with larger HRQL decline during follow up (-4.04 ± 2.02 points per logarithm liver volume, P = 0.049). In autosomal dominant polycystic kidney disease, patients with large liver and kidney volumes had larger decline in HRQL (5.36 ± 2.54 points per logarithm liver volume; P = 0.040 and -4.00 ± 1.88 per logarithm kidney volume; P = 0.039). CONCLUSION: Somatostatin analogues improve HRQL in symptomatic polycystic liver disease. Halting the progressive nature of polycystic liver disease is necessary to prevent further decline of HRQL in severe hepatomegaly.

Antiviral therapy in chronic hepatitis E: a systematic review.

Hepatitis E viral infection can lead to a chronic infection in immunocompromised patients, resulting in progressive liver disease and cirrhosis. Isolated cases have shown that treatment with ribavirin or pegylated interferon-α can result in viral eradication. This systematic review evaluated efficacy and safety of both treatments in chronic hepatitis E. A systematic literature search was performed on PubMed, Web of Science and clinicaltrials.gov for articles and abstracts. The keywords '"Hepatitis E" or HEV' AND 'ribavirin or Rebetol or Copegus' OR 'pegylated interferon OR peginterferon' were combined. The primary outcome was sustained viral response (SVR). Secondary endpoints include rapid viral response (RVR), relapse rates and side effects. Twenty-four studies matched our criteria, representing a total of 105 ribavirin-treated and 8 pegylated interferon-treated patients. The majority of patients had a solid organ transplant. Sixty-four per cent of ribavirin-treated patients achieved a SVR at 6 months after treatment cessation compared to 2/8 peginterferon-treated patients. Ribavirin was relatively well tolerated with the main side effect being anaemia, requiring dose reduction in 28% of patients. Peginterferon leads to acute transplant rejection in 2/8 patients. Ribavirin monotherapy appears to be an effective and safe treatment in all immunocompromised patients with chronic hepatitis E. The use of pegylated interferon in transplant patients may lead to transplant rejection and is not recommended. Therefore, ribavirin should be the antiviral treatment of choice in chronic hepatitis E.

Systematic review: the management of hepatic cyst infection.

BACKGROUND: Cyst infection is a severe complication of hepatic cystic disease. However, an evidence-based treatment strategy is not available. AIM: To assess the available treatment strategies and provide a treatment advice for de novo hepatic cyst infection. METHODS: We systematically searched PubMed (1948-2014), EMBASE (1974-2014), and the Cochrane Library (until 2014) for studies involving humans (≥18 years) treated for a hepatic cyst infection. We extracted data on patient characteristics, treatment and follow-up. RESULTS: We identified 41 articles; all were case series or case reports, implicating a high risk of bias. We included 54 hepatic cyst infection cases (male 39%; mean age 63 ± 12 years; diabetes 6%; dialysis 19%; transplant recipients 30%). Initial therapy consisted of antimicrobial (56%), percutaneous (31%) or surgical treatment (13%). We identified 42 antimicrobial regimens consisting of 23 different combinations. Most used antibiotic classes were quinolones (34%) and cephalosporins (34%). Antimicrobials failed in 70% of cases, eventually requiring percutaneous or surgical treatment in, respectively, 37% and 27%. Recurrent hepatic cyst infection was frequent (20%). Median time to recurrence was 8 weeks (IQR 3-24 weeks). In 46%, recurrence occurred in renal transplant recipients. Cyst infection related deaths occurred in 9%, of whom 40% were on dialysis. CONCLUSIONS: The literature shows that treatment of hepatic cyst infection is highly heterogeneous. We recommend first line treatment with oral ciprofloxacin. In case of failure, percutaneous cyst drainage needs to be considered.

Safety and efficacy of different lanreotide doses in the treatment of polycystic liver disease: pooled analysis of individual patient data.

BACKGROUND: Long-acting lanreotide (LAN) 120 mg every 4 weeks reduces liver volume (LV) in patients with polycystic liver diseases (PCLD). Animal studies demonstrated that the inhibition of hepatic and renal cystogenesis is dose dependent. AIM: To investigate the safety and efficacy of two different LAN doses in PCLD patients. METHODS: The 6-month results of the LOCKCYST I trial, its extension study and the LOCKCYST II trial were pooled. LV at baseline and month 6 was measured by CT-scan and blindly re-analysed by two independent radiologists. RESULTS: The study population [132 treatment periods, age 49 years (IQR: 45-55), 114 women] consisted of three groups. Each received treatment every 4 weeks during 6 months: placebo (n = 26); LAN 90 mg (n = 55) or LAN 120 mg (n = 51). The inter-observer variability and agreement in the calculation of LV were excellent. Severe side effects occurred with placebo, LAN 90 mg and LAN 120 mg in respectively 0%, 7% and 16%. Change in LV's after 6 months in these three groups were respectively: increase of +36 mL [(-45)-(+138)]; decrease of -82 mL [(-285)-(+92)] and decrease of -123 mL [(-312)-(+4)] (Kruskal-Wallis One Way anova on Ranks; P = 0.002). Based on ROC analysis, a reduction of ≥120 mL in LV has a positive predictive value of 64% for improving symptoms (ROC analysis AUC: 0.729; sensitivity 73%, specificity 69%, P < 0.0001). CONCLUSIONS: Both LAN 90 mg and LAN 120 mg reduce liver volume. LAN 90 mg has less side effects. This suggests that in case of intolerance to LAN 120 mg, a dose reduction to LAN 90 mg is meaningful.

The long-term outcome of patients with polycystic liver disease treated with lanreotide.

BACKGROUND: Polycystic liver disease (PLD) is a phenotypical expression of autosomal dominant polycystic kidney disease and isolated polycystic liver disease. Somatostatin analogues, such as lanreotide, reduce polycystic liver volume. AIM: To establish long-term outcome and safety of lanreotide. METHODS: This was an open-label, observational extension study of a 6-month, randomised, placebo-controlled trial with lanreotide (120 mg/month) in PLD. The length of total treatment was 12 months. Primary endpoint was relative change in liver volume, as determined by CT-volumetry after 12 months of treatment. We offered patients a CT scan 6 months after stopping lanreotide. RESULTS: A total of 41/54 (76%) patients participated in the extension study. Liver volume decreased by 4% (IQR -8% to -1%) after 12 months of treatment. The greatest effect was observed during the first 6 months of treatment (decrease of 4% (IQR -6% to -1%)). Liver volume remained unchanged during the following 6 months. We found that liver volume increased by 4% (IQR 0-6%) 6 months after end of treatment (n = 22). CONCLUSIONS: Lanreotide reduces liver volume within the first 6 months of treatment and the beneficial effect is maintained in the following 6 months. Stopping results in recurrence of polycystic liver growth. This suggests that continuous use of lanreotide is needed to maintain its effect.

Hepatic and renal manifestations in autosomal dominant polycystic kidney disease: a dichotomy of two ends of a spectrum.

Autosomal dominant polycystic kidney disease (ADPKD) is a multisystem disorder. It is the most common genetic cause of end-stage renal disease. One frequent extra-renal manifestation is hepatic cyst formation. The majority of ADPKD patients develop complications as a result of renal cyst formation; however, a small proportion develop extensive hepatic disease with minor renal features. Both phenotypes seem to represent the spectrum of ADPKD. This review discusses the current understanding of the pathogenesis of the disease, its manifestations and the mechanisms of cyst formation. Furthermore, it focuses on monitoring the disease and the treatment options currently available.

Treatment extension benefits HCV genotype 1 patients without rapid virological response: a systematic review.

BACKGROUND: Current guidelines recommend 48 weeks of treatment with pegylated interferon and ribavirin for patients infected with chronic hepatitis C virus (HCV) genotype 1. Several clinical trials have investigated the efficacy of treatment duration longer than 48 weeks, but yielded discordant results. METHODS: We performed a structured search of PubMed, Web of Science and the Cochrane library to identify randomised clinical trials in HCV genotype 1 patients who were treated either for 48 or 72 weeks. Sustained viral response (SVR) data were pooled and a sample size weighted pooled proportion was calculated. RESULTS: We identified five studies matching our criteria. Studies randomised at baseline (n=1), at absence of rapid virological response (RVR) at week 4 (n=1), at early virological response at week 12 (EVR) (n=1) or at slow response at week 24 (n=2). In the RCT that randomised at absence of RVR, SVR was significantly higher in the extended treatment arm (57 vs 42%, p=0.02) with an RR of 1.35 (95% CI 1.04 to 1.75). This tendency was also observed in the studies that randomised at slow response (44 vs 35%), although no longer statistically significantly different. CONCLUSION: Prolonged 72-week treatment should be considered in HCV genotype 1 patients without RVR at week 4, as this increased SVR.

Edge and corner detection by photometric quasi-invariants.

Feature detection is used in many computer vision applications such as image segmentation, object recognition, and image retrieval. For these applications, robustness with respect to shadows, shading, and specularities is desired. Features based on derivatives of photometric invariants, which we will call full invariants, provide the desired robustness. However, because computation of photometric invariants involves nonlinear transformations, these features are Instable and, therefore, impractical for many applications. We propose a new class of derivatives which we refer to as quasi-invariants. These quasi-invariants are derivatives which share with full photometric invariants the property that they are insensitive for certain photometric edges, such as shadows or specular edges, but without the inherent instabilities of full photometric invariants. Experiments show that the quasi-invariant derivatives are less sensitive to noise and introduce less edge displacement than full invariant derivatives. Moreover, quasi-invariants significantly outperform the full invariant derivatives in terms of discriminative power.

PicToSeek: combining color and shape invariant features for image retrieval.

We aim at combining color and shape invariants for indexing and retrieving images. To this end, color models are proposed independent of the object geometry, object pose, and illumination. From these color models, color invariant edges are derived from which shape invariant features are computed. Computational methods are described to combine the color and shape invariants into a unified high-dimensional invariant feature set for discriminatory object retrieval. Experiments have been conducted on a database consisting of 500 images taken from multicolored man-made objects in real world scenes. From the theoretical and experimental results it is concluded that object retrieval based on composite color and shape invariant features provides excellent retrieval accuracy. Object retrieval based on color invariants provides very high retrieval accuracy whereas object retrieval based entirely on shape invariants yields poor discriminative power. Furthermore, the image retrieval scheme is highly robust to partial occlusion, object clutter and a change in the object's pose. Finally, the image retrieval scheme is integrated into the PicToSeek system on-line at http://www.wins.uva.nl/research/isis/PicToSeek/ for searching images on the World Wide Web.